Bromo-Adenosine Stimulates Choriogonadotropin Production in JAr and Cytotrophoblast Cells: Evidence for Effects on Two Stages of Differentiation

Abstract

8-Bromo-adenosine (8-Br-adenosine) stimulates CG production in the JAr choriocarcinoma cell line. Because production of the alpha and beta CG subunits is coupled to the differentiation state of the trophoblasts, we compared the effect of adenosine on CG synthesis in the choriocarcinoma cell line with that in cytotrophoblast cells isolated from normal human term placenta. 8-Br-adenosine stimulated CG production by 5- to 6-fold in both cell types, whereas 8-Br-guanosine had no effect, demonstrating specificity for adenine-containing derivatives. The ratio of CG alpha to CG beta production in JAr cells was 2:1 in the absence or presence of 8-Br-adenosine, whereas in cytotrophoblasts the ratio was 14:1 in controls, but decreased to 3:1 with 8-Br-adenosine. The latter is attributed to an enhanced production of the beta-sub-unit. Immunocytochemistry revealed that CG alpha and CG beta were only expressed in about 4% of JAr cells, and 8-Br-adenosine stimulated the number of positive cells 2- to 4-fold. Since 8-Br-adenosine also inhibited the division of JAr cells, the data suggest that it stimulates CG expression by promoting exit of a population of the cells from the cell cycle. In nondividing placenta-derived cytotrophoblasts, 8-Br-adenosine affects a later step in the differentiation pathway, resulting in a greater effect on the beta- than the alpha-subunit. Thus, our data further support the hypothesis that regulation of CG biosynthesis is linked to differentiation of the trophoblast.